title: Functions and regulation of MUC13 mucin in colon cancer cells.
abstract: BACKGROUND
  MUC13 is overexpressed and aberrantly localized in colon cancer tissue; however, the specific functions and regulation of MUC13 expression are unknown.
  
  
  METHODS
  Stable cell lines with either overexpressed or suppressed MUC13 levels were analyzed to determine cell growth, colony formation, cell migration, and cell invasion assays. The molecular mechanisms involved in MUC13 regulation were elucidated via chromatin immunoprecipitation (ChIP) and analysis of interleukin 6 (IL6) treatments. Colon cancer tissues were analyzed by immunohistochemistry (IHC) for the protein levels of MUC13 and P-STAT5 in colon cancer cells.
  
  
  RESULTS
  Overexpression of MUC13 increased cell growth, colony formation, cell migration, and invasion. In concordance, MUC13 silencing decreased these tumorigenic features. Overexpression of MUC13 also modulated various cancer-associated proteins, including telomerase reverse transcriptase, sonic hedgehog, B cell lymphoma murine like site 1, and GATA like transcription factor 1. Additionally, MUC13-overexpressing cells showed increased HER2 and P-ERK expression. ChIP analysis revealed binding of STAT5 to the predicted MUC13 promoter. IL6 treatment of colon cancer cells increased the expression of MUC13 via activation of the JAK2/STAT5 signaling pathway. Suppression of JAK2 and STAT5 signaling by chemical inhibitors abolished IL6-induced MUC13 expression. IHC analysis showed increased expression of both P-STAT5 and MUC13 in colon cancer as compared to adjacent normal tissue.
  
  
  CONCLUSIONS
  The results of this study, for the first time, suggest functional roles of MUC13 in colon cancer progression and provide information regarding the regulation of MUC13 expression via JAK2/STAT5 which may reveal promising therapeutic approaches for colon cancer treatment.
authors.affiliation: Cancer Biology Research Center, Sanford Research/USD, 2301 E, 60th Street N, Sioux Falls, SD, 57104, USA.
authors.forename: Brij K
authors.initials: BK
authors.lastname: Gupta
authors.forename: Diane M
authors.initials: DM
authors.lastname: Maher
authors.forename: Mara C
authors.initials: MC
authors.lastname: Ebeling
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Stephenson
authors.forename: Susan E
authors.initials: SE
authors.lastname: Puumala
authors.forename: Michael R
authors.initials: MR
authors.lastname: Koch
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
mesh_terms: D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050799:STAT5 Transcription Factor / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D015850:Interleukin-6; C429552:MUC13 protein, human; D009077:Mucins; D009363:Neoplasm Proteins; D050799:STAT5 Transcription Factor